Background Keshan disease （KD） is an endemic cardiomyopathy in China.The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease.Young women of child-bearing age are the most frequent victims in rural areas.The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.Methods We extracted RNA from the peripheral blood mononuclear cells of KD patients （12 women and 4 men） and controls （12 women and 4 men）.Then the isolated RNA was amplified,labeled and hybridized to Agilent human 4×44k whole genome microarrays.Gene expression was examined using oligonucleotide microarray analysis.A quantitative polymerase chain reaction assay was also performed to validate our microarray results.Results Among the genes differentially expressed in female KD patients we identified：HLA-DOA,HLA-DRA,and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7,involved in cardiomyocyte differentiation defect; and ADAMTS 8,CCL23,and TNFSF15,implicated in anti-angiogenic activities.These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.Conclusion Our results might help to explain the higher susceptibility of women to this disease.
Few effective treatments for chronic Keshan disease have been available till now.The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive.This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up.A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years.Of the 302 chronic Keshan disease patients,170(56.3%)were given selenium supplementation until the end point of follow-up.Cox proportional hazards regression models were used to identify the independent predictors of cardiac events.Our results showed that during the follow-up,there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group(101/170,59.4%)and 98 in non-selenium supplementation group(98/132,74.2%).Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death(HR 0.39,95%CI 0.28-0.53)after adjustment for baseline age,sex,cigarette smoking,family history of Keshan disease,body mass index(BMI),heart rate,electrocardiogram(ECG)abnonnalities,blood pressure,initial cardiothoracic ratio,left ventricular可ection fractions(LVEF)and whole-blood selenium concentration.Our ten-year follow-up analysis indicated that selenium supplementation,specifically combined with the use of angiotensinconverting cnzyme inhibitor and beta blocker therapy,improved the survival of patients with chronic Keshan disease with congestive heart failure.BMI,selenium deficiency,male,combined ECG abnonnalities,LVEF,and fast heart rate increased the risk of cardiac events.
In this study, differentially expressed genes in peripheral blood from patients with Kashin-Beck disease and Keshan disease were compared to further investigate the etiology and pathogenesis of both diseases, which occur in a common endemic area of China. Twenty Kashin-Beck disease patients and 12 healthy controls, and 16 Keshan disease patients and 16 healthy controls, were grouped into four pairs. Patients and controls were selected from common endemic areas for the two diseases. Total RNA was isolated from peripheral blood mononuclear cells from all patients and controls, and gene expression profiles analyzed by oligonucleotide microarrays. Sixteen genes differentially expressed in both Kashin-Beck disease and Keshan disease (versus controls) were identified, and comprised nine genes showing synchronous and seven asynchronous expression. The Comparative Toxicogenomics Database shows that expression and biological function of these genes can be affected by multiple environmental factors, including mycotoxin and selenium content, potential environmental risk factors for the two diseases. Thus, these shared differentially expressed genes may contribute to the distinct organ lesions, caused by common environmental risk factors of Kashin-Beck disease and Keshan disease.
